Diisopropylethylamine → 1,1-Dimethylethyl ((3R)-1-{[4-(methylamino)-3-nitrophenyl]carbonyl}-3-piperidinyl)carbamate

HRID 2275004Notes

Reaction equation

HRID 2275004 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.[CH3:15][NH:16][C:17]1[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][C:18]=1[N+:26]([O-:28])=[O:27].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C)C=O.CCOCC.O>[C:10]([O:9][C:8](=[O:14])[NH:7][C@@H:3]1[CH2:4][CH2:5][CH2:6][N:1]([C:21](=[O:22])[C:20]2[CH:24]=[CH:25][C:17]([NH:16][CH3:15])=[C:18]([N+:26]([O-:28])=[O:27])[CH:19]=2)[CH2:2]1)([CH3:11])([CH3:13])[CH3:12]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2834754-(Methylamino)-3-nitrobenzoic acidHCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 863401791,1-Dimethylethyl ((3R)-1-{[4-(methylamino)-3-nitrophenyl]carbonyl}-3-piperidinyl)carbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-tert-butyl piperidin-3-ylcarbamate (1.460 g, 7.29 mmol) (available from, for example, Apollo Scientific Ltd), 4-(methylamino)-3-nitrobenzoic acid (1.43 g, 7.29 mmol) and HATU (2.77 g, 7.29 mmol) in N,N-dimethylformamide (DMF) (50 mL) was added DIPEA (2.55 mL, 14.58 mmol) and the reaction stirred at r.t. for 16 h. Water (200 mL) and Et2O (200 mL) were added and the layers separated. The aqueous layer was extracted with further Et2O (2×200 mL) and the combined organics washed with water (2×50 mL), dried (Na2SO4) and concentrated in vacuo to afford a bright yellow oil. The crude product was purified on silica (100 g) using a gradient of 40% EtOAc/cyclohexane→100% ethyl acetate/cyclohexane. The appropriate fractions were combined and evaporated under vacuum to give the title product as an orange-gold solid (2.76 g, 7.29 mmol, 100% yield).

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted with further Et2O (2×200 mL)
  3. washthe combined organics washed with water (2×50 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customto afford a bright yellow oil
  7. customThe crude product was purified on silica (100 g)
  8. customevaporated under vacuum

Sources & evidence

ORD record
ord-b09049faa94749bb81b767237a152d99
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

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